MECHANISM OF ACTION & KEY DATA

APIM Therapeutics is developing a pipeline of peptide compounds engineered to penetrate cells and target PCNA
in both nucleus and the cytoplasm. ATX-101, the company’s current lead
compound, is a first-in-class, chemically synthesized peptide targeting PCNA/APIM
interactions formed upon DNA Damage Response. ATX-101 acts at three
different levels:

ATX-101, the company’s current lead compound is currently being developed for the treatment of several cancer indications either alone or in combination with selected anti-cancer agents. A snapshot of the drug pipeline of APIM Therapeutics is presented below. The company has a strong interest in bladder cancer (localized/superficial and advanced) and multiple myeloma. Other indications/combinations are also of further interest for future applications. For a first-in-man study, APIM Therapeutics will focus on a phase I/IIa study in advanced cancer patients (intravenous administration). The study will start in early 2018.

Based on this mechanism of action, APIM-peptides are predicted to
improve the therapeutic index of existing therapies by:

Increasing the efficacy of current anti-cancer
agents without a concomitant rise in toxicity and

Overall, ATX-101 shows a strong
combinatorial capacity in vitro and in vivo.

About PCNA
PCNA is currently recognized as a "hub" protein interacting with a wide network of proteins involved in the DNA Damage Response (e.g. proteins involved in DNA repair, chromatin remodeling/ epigenetic & cell cycle control, signal transduction and apoptosis). During normal replication, proteins which facilitate replication interact with PCNA through a peptide sequence known as the PIP-box. However, under conditions of DDR stress, there is a switch in the affinity of proteins interacting with PCNA from those which, under normal conditions, interact via the PIP-box motif to those involved in coping with stress through an interaction via the APIM motif. Via this "stress-switch" response, PCNA ultimately controls cellular responses to several stress inducing agents including a wide range of chemotherapeutic and targeted agents.

About APIM-motifThe APIM-motif is present in a large number of proteins involved in
the DNA Damage Response (e.g. in genome maintenance, cell cycle control and signal transduction). By incorporating the APIM motif in a peptide drug, several cellular defense systems dealing with stress are simultaneously impaired. This results in hypersensitivity to many anti-cancer treatments as well as induction of rapid apoptosis in cancer cells treated with APIM-peptides as single agents.